Is Neutrophil Gelatinase–Associated Lipocalin an Optimal Marker of Renal Function and Injury in Liver Transplant Recipients?

Background

Recently, research has focused on the association of neutrophil gelatinase–associated lipocalin (NGAL) with acute and/or active kidney injury. However, it should be remembered that NGAL is involved in iron metabolism and antimicrobial defense mechanisms.

Methods

One hundred seven consecutive liver transplant recipients were included in this study. Plasma and urine NGAL levels were measured with the use of enzyme-linked immunosorbent assay. NGAL levels were studied as plasma concentrations (pNGAL), urine concentrations (uNGAL), urinary NGAL to creatinine ratio (uNGAL/Cr), and fractional NGAL secretion (fNGAL).

Results

pNGAL was found to be inversely correlated with estimated glomerular filtration rate (eGFR) and plasma cystatine C (pCysC) (r = −0.26 and P = .007, r = −0.38 and P = .00006, respectively). uNGAL was positively correlated with urinary cystatine C to creatinine ratio (uCysC/Cr) and fractional cystatine C excretion (fCysC) (r = 0.43 and P = .000004; r = 0.4 and P = .1; respectively). uNGAL/Cr was inversely correlated with hematocrit (Htc) and hemoglobin (Hb) (r = −0.35 and P = .0002; r = −0.39 and P = .00004; respectively), and positively correlated with uCysC/Cr (r = 0.5 and P < .0000001). fNGAL was directly correlated with uCysC/Cr and fCysC (r = 0.53 and P < .0000001; r = 0.39 and P = .00005; respectively) and inversely correlated with red blood cell count (RBC; r = −0.31 and P = .001). We observed significant differences of pNGAL, uNGAL/Cr, and fNGAL between sexes, with highest values of uNGAL, uNGAL/Cr, and fNGAL in women and pNGAL in men. In multivariate regression analysis, pNGAL was positively correlated with time elapsed from liver transplantation, neutrophil count, pCysC, and sex (β = 0.36 and P = .00001; β = 0.32 and P = .0001; β = 0.58 and P < .0000001; β = 0.17 and P = .025; respectively) and inversely correlated with patient's age (β = −0.18 and P = .02) with R = 0.67 and R² = 0.45, independently from blood glucose, eGFR, RBC, white blood cell count, Hb, uCysC, uCysC/Cr, and fCysC.

Conclusions

Plasma and urine NGAL levels are strongly correlated not only with kidney function parameters, but also with red and white blood cell parameters and patient's age and sex.     

Do Antithymocyte Globulin-Free Acute Rejection Therapies Increase the Risk of Polyoma Nephropathy in Renal Transplant Recipients?

IntroductionBK virus nephropathy is a serious complication that can lead to allograft kidney loss. Excessive immunosuppression increases the risk. We aimed to evaluate whether there is an increased risk of BK viremia and nephropathy in patients who underwent high-dose immunosuppression because of the development of acute rejection in the early period after kidney transplantation.MethodsThis retrospective cohort study was performed between April 2015 and March 2016. Twenty-nine patients who had biopsy-proven acute rejection in the first 3 months were evaluated for BK viremia and nephropathy. Thirty patients who had transplantations at the same period were the control group. Plasma BK-DNA values were examined at 1, 2, 3, 6, 9, and 12 months after the rejection treatment and at 3, 6, 9, and 12 months in the control group. Presence of polyoma nephropathy was examined with surveillance biopsies at the 6 and 12 months.ResultsAcute rejection treatment was started on the 12th day after transplantation (2–37 days). Seventeen cellular rejections and 12 humoral rejections were reported by biopsy. Two of the 12 humoral rejections were suspicious. Only pulse steroid (PS) (n = 18); PS, plasmapheresis, and intravenous immunoglobulin (n = 8); PS and intravenous immunoglobulin (n = 2); and PS and plasmapheresis (n = 1) treatments were performed. In 21 patients in the rejection group and 25 patients in the control group, BK-DNA was not positive at all. Two patients had graft loss at 11 and 36 months in the rejection group. Graft losses were secondary to rejection.ConclusionsTreatment with antithymocyte globulin-free regimens after acute rejection episodes did not lead to an increase in BK viremia.     

Sirolimus: A Switch Option for Mycophenolate Mofetil–Induced Leukopenia in Renal Transplant Recipients

Mycophenolate mofetil (MMF) is a potent immunosuppressive agent used to prevent acute and chronic rejection in kidney transplantation or for rescue therapy. One side effect of MMF is bone marrow toxicity, including leukopenia, which may necessitate drug withdrawal. We report 2 patients who underwent kidney transplantation and developed leukopenia while receiving MMF and safely switched to sirolimus. A 35-year-old woman underwent deceased donor kidney transplantation. She received basiliximab, tacrolimus, MMF, and a corticosteroid. On postoperative day (POD) 75, her white blood cell (WBC) count was 1800/μL. A 44-year-old women underwent deceased donor kidney transplantation and received basiliximab, tacrolimus, MMF, valganciclovir, and a corticosteroid. On POD 88, her WBC count was 1320/μL. MMF was switched to sirolimus, resulting in recovery of WBC count without rejection. Switch from MMF to sirolimus is safe and favorable in MMF-induced leukopenia in renal transplant recipient.     

Cystatin C–Based Equation for Predicting the Glomerular Filtration Rate in Kidney Transplant Recipients

Background

Precise monitoring of the glomerular filtration rate (GFR) is needed to estimate the allograft function in kidney transplant recipients (KTRs). The GFR is widely estimated with the use of formulas based on serum cystatin C (SCys) and serum creatinine (SCr) levels. We compared the efficacy of SCys-based equations with that of SCr-based equations to predict the allograft function.

High Incidence of Rejection Episodes and Poor Tolerance of Sirolimus in a Protocol With Early Steroid Withdrawal and Calcineurin Inhibitor–Free Maintenance Therapy in Renal Transplantation: Experiences of a Randomized Prospective Single-Center Study

Immunosuppressive maintenance therapy after kidney transplantation leads to various undesired side effects such as calcineurin inhibitor (CNI)–associated nephrotoxicity or elevated cardiovascular risk due to posttransplantation diabetes and hypertension. These effects show negative impacts on long–term allograft function as well as patient morbidity and mortality. Therefore, we used an immunosuppressive regimen with early corticosteroid withdrawal (ESW), maintenance therapy containing tacrolimus, sirolimus (SRL), and mycophenolate sodium for 3 months followed by a prospective randomized trial comparing a CNI free versus a low-dose CNI therapy. The primary endpoint was 6-month graft function. Among 75 patients, ESW was performed after 4 days in 65 patients. Over the following 3 months before randomization to CNI-free maintenance therapy, we experienced a high number (25%) of SRL discontinuations due to adverse events, including leukopenia, anemia, arthritis, and pneumonitis. In addition there were significantly more allograft rejection episodes in the CNI-free group (P = .017) during the study period leading to a switch from SRL to a CNI. Despite the higher rate of rejection episodes in the CNI-free groups, glomerular filtration rates (GFR) at 6 months were comparable between the study groups (P = .25). After 1 year only 9.2% (6/65) of all patients treated with SRL remained on this drug. Conclusion, there was an unacceptably high rate of SRL intolerance using an ESW and CNI-free immunosuppressive regimen combined with a significantly higher rate of rejection episodes.     

Wünderlich Syndrome in Renal Transplant Recipients: A Case Report and Literature Review

BackgroundWünderlich syndrome, or spontaneous atraumatic renal hemorrhage, is a clinical entity rarely described in the native kidney of patients who have undergone renal transplant. Although its manifestation is quite similar in reported cases, it may present few symptoms, from bleeding of unidentified etiology to dramatic pictures associated with hypovolemic shock. There are few reports of spontaneous hemorrhage of a native kidney after kidney transplantation.Case reportWe present a 38-year-old male patient who developed hemorrhage of a ruptured native kidney after a late renal transplantation. We analyze what has been reported in the literature and highlight the possibility of this complication after kidney transplantation. Imaging exams and surgical specimen demonstrated the presence of ruptured angiomyolipoma in the patient's native right kidney. The postoperative period was not complicated, with a benign clinical evolution.ConclusionAlthough rare in patients who have undergone renal transplant, it is justified to suggest Wünderlich syndrome in the presence of acute flank pain, abdominal tenderness, and signs of internal bleeding (Lenk's triad), with unexplained hemoglobin drop.     

Is There Any Association Between Triglyceride–Glucose Index and Graft Function in Kidney Transplant Recipients?

BackgroundAlthough previous studies have illustrated the relationship between chronic kidney disease, coronary artery disease, erectile dysfunction, and the triglyceride–glucose index (TyGi), the relationship between this index and postoperative graft function in patients undergoing renal transplantation has yet to be investigated. In the present study, we aimed to reveal the association between the TyGi and renal graft outcomes in patients who underwent renal transplantation.MethodsWe retrospectively collected data on living and cadaveric kidney donor recipients between May 2019 and April 2022. The recipients’ age, sex, body mass index, preoperative fasting glucose and triglyceride levels, TyGi, estimated glomerular filtration rate (eGFR), and serum creatinine measurement data were recorded. The patients were divided into 2 groups according to their GFR values (group 1: GFR <60 mL/min/1.73 m²; group 2: GFR ≥60 mL/min/1.73 m²). Follow-up serum creatinine–eGFR levels and TyGi measurements were compared between the recipients in group 1 and group 2.ResultsThe mean TyGi measurements of the recipients were 8.79 ± 0.64 in group 1 and 8.83 ± 0.72 in group 2. There was no statistically significant difference in terms of the TyGi measurements between the 2 groups (P >. 05). No statistically significant correlation was found between the recipients’ creatinine, eGFR, and TyGi at 1st, 6th, and 12th postoperative months (P > .05).ConclusionsWe believe that the relationship between the TyGi and renal graft function can be more clearly understood in prospective studies that include a higher number of patients and a longer follow-up period.     

Fibroblast Growth Factor–23 Levels Are Associated With Uric Acid But Not Carotid Intima Media Thickness in Renal Transplant Recipients

IntroductionCardiovascular disease (CVD) is the leading cause of mortality in chronic kidney disease (CKD) patients. Fibroblast growth factor–23 (FGF-23) is associated with atherosclerosis and cardiovascular mortality in CKD patients and healthy subjects. However, data in renal transplant recipients (RTR) are scarce. We aimed to determine factors associated with FGF-23 and to explore its relationship to atherosclerosis.MethodsForty-six patients and 44 controls were included. FGF-23 was measured from plasma. Carotid intima media thickness (CIMT) was evaluated ultrasonographically.ResultsPatients had higher waist circumference (WC; 92.2 ± 14.9 vs 85.3 ± 11.0 cm; P < .05), glucose (99.8 ± 17.2 vs 90.3 ± 6.5 mg/dL; P < .01), creatinine (1.43 ± 0.6 vs 0.86 ± 0.1 mg/dL; P < .01), triglyceride (160.4 ± 58.9 vs 135.6 ± 59.8 mg/dL; P < .05), white blood cells (WBC; 7938.6 ± 2105.2 vs 6715.7 ± 1807.5 WBC/mm³; P < .01), ferritin (217.0 ± 255.8 vs 108.3 ± 142.4 ng/mL; P < .05), uric acid (6.5 ± 1.6 vs 4.7 ± 1.3 mg/dL; P < .01), C-reactive protein (CRP; 8.2 ± 18.2 vs 5.3 ± 7.9 mg/L; P < .01), parathyroid hormone (PTH; 89.7 ± 59.2 vs 44.1 ± 16.7 pg/mL; P < .01), and alkaline phosphatase (ALP; 162.5 ± 86.6 vs 74.2 ± 21.9 U/L; P < .01). FGF-23 was higher in patients (11.7 ± 7.2 vs 9.6 ± 6.8 pg/mL; P < .05). CIMT was similar (0.58 ± 0.09 vs 0.57 ± 0.1 mm; P > .05). WC, creatinine, and uric acid were positively correlated with FGF-23, whereas albumin showed negative correlation. On multivariate analysis only creatinine and uric acid were determinants of FGF-23.ConclusionFGF-23 levels are associated with uric acid in RTR. Larger studies are needed to confirm this finding.     

Low Body Mass Index in Kidney Transplant Recipients: Risk or Advantage for Long-Term Graft Function?

OBJECTIVES: Nutritional status is known to be a marker of overall health status and a strong predictor of patient survival in several diseases. Whereas obesity is suspected to have a negative influence on general renal transplantation outcomes, the relationship between impaired nutritional status and long-term kidney graft survival is not yet clear. METHODS: We retrospectively analyzed graft survival with a follow-up time of 5 to 12.5 years among 224 kidney transplantations. A Cox proportional hazards model was applied to estimate risk factors for loss of graft function. RESULTS: The Cox model initially showed no significant influence of the body mass index (BMI) at 1 year after transplantation on the risk of transplant failure (relative risk 0.97 per BMI unit, P = .34). When the patients were divided into two groups according to BMI, a clear disadvantage was shown in terms of long-term graft survival for the groups with a low BMI. The risk of loss of transplant function increased by a factor of 1.85 (relative risk) if the BMI 1 year after kidney transplantation was less than 23 (P = .035). CONCLUSIONS: These findings suggested impaired long-term kidney graft survival among patients with reduced nutritional status. This result is assumed to reflect improved immune function due to reduced nutrient availability, thus leading to reinforcement of chronic rejection processes. This assumption is consistent with the already known immunomodulatory effect of caloric restriction to mitigate T-cell activation.     

Is Screening for IgG Antibody to Cytomegalovirus and Epstein-Barr Virus Infections Mandatory in Potential Renal Transplant Recipients and Donors in Iran?

Objective

Cytomegalovirus (CMV) and/or Epstein-Barr virus (EBV) infections in renal transplant recipients may cause significant morbidity and mortality. To manage these infections, established guidelines suggest that both the recipient and the donor be routinely tested for anti-CMV and anti-EBV antibodies prior to renal transplantation. The aim of this study was to assess the value of screening among people living in Iran.

Patients and Methods

We retrospectively analyzed the incidences of CMV and EBV infections among 925 and 710 potential renal allograft donors and recipients, respectively, between 2005 and 2008. All cases were first transplantations. Enzyme-linked immunosorbent assays (ELISA) were performed to determine whether there were antibodies to CMV (IgG) or EBV viral capsid antigen (VCAIgG). Finally, we analyzed the seroprevalence and demographic factors.

Results

Five hundred sixty-eight (61.40%) potential renal transplant donors and 483 (68.02%) potential renal transplant recipients were men. Donor ages ranged from 18 to 50 years (mean ± SD, 34.7 ± 8.1 years) and recipient ages ranged from 18 to 60 years (mean ± SD, 45.9 ± 7.3 years). Pretransplant CMV (IgG) and EBV (VCAIgG) seroprevalence was 100% among all donor, and recipient ages and sexes.

Conclusion

Our findings suggested that kidney transplant centers in Iran do not need to perform routine screening for IgG antibodies to CMV and EBV among renal transplant recipients and donors of ages ≥18 years.     

Serum Levels of S100β, Neuron-Specific Enolase,Glial Fibrillary Acidic Protein in Kidney Transplant Recipients and Donors: A Prospective Cohort Study

BackgroundThe aim of this study was to evaluate changes in serum levels of S100β, neuron-specific enolase, glial fibrillary acidic protein in living donors and recipients after kidney transplantation.MethodsWe enrolled 56 patients into the study. Of these, 27 underwent donor nephrectomy (group D), and the remaining 29 underwent kidney transplantation (recipient, group R). Neuromarkers were measured in samples obtained before the procedure, on postoperative day 7, and at 1 month postoperatively.ResultsPostoperative kidney functions were impaired in patients who underwent living donor nephrectomy compared with their preoperative levels (P < .001), although no significant difference was observed in their neuromarkers. The postoperative delirium rating scale was also impaired after living donor nephrectomy compared with preoperative levels (P < .05). Postoperative kidney functions were improved (P < .001), and a progressive decrease in neuromarker levels (P < .05) was observed in kidney transplant recipients compared with their preoperative levels. Linear regression analysis showed a significant correlation between neuron-specific enolase, glial fibrillary acidic protein levels and kidney functions in recipients.ConclusionThe present study demonstrated that neuron-specific enolase and glial fibrillary acidic protein levels decrease in kidney transplant recipients and do not change in donors. This result indicated that there is no evidence of neurotoxicity in either recipients and donors in kidney transplantation.     

Is There a Correlation with Pre-donation Kidney Volume and Renal Function in the Renal Transplant Recipient?: A Volumetric Computed Tomography Study

PurposeThe aim of this study is to determine the correlation between the predonation computed tomography (CT)-based calculated kidney volume and post-transplant renal function in recipients of renal transplants and to compare two different CT techniques.Material and methodsThe study group is comprised of 55 paired living kidney donor-recipients transplants. The total parenchymal renal volumes were calculated by using two CT-based techniques (3-dimensional renal volume [3DRV] and voxel-based volume calculation). Post-transplant creatinine and estimated glomerular filtration rate (eGFR) levels for the recipients at hospital discharge and sixth month were obtained. We tested the association with eGFR and creatinine by adjusting the renal volume to body weight and body mass index. For the creatinine levels above 1.5 mg/dL at discharge, a threshold value for renal volume-to-weight ratio on receiver operating characteristic curve (ROC) analysis and odds ratio (OR) were calculated.ResultsThe renal volumes adjusted to weight were found to be moderately correlated with eGFR and creatinine levels at discharge (r = 0.51 and r = −0.54 for voxel-based calculation; r = 0.52 and r = −0.52 for 3DRV calculation, P < .001, respectively) and at sixth month (r = 0.55 and r = −0.58 for voxel-based calculation; r = 0.51 and r = −0.54 for 3DRV calculation, P < .001 respectively). A threshold value of 1.84 mL/kg was calculated for parenchymal volume-to-recipient weight ratio on ROC analysis (AUC±SE, 0.760 ± 0.078, P = .008). The likelihood of creatinine elevation above 1.5 mg/dL was found to be nine times greater for smaller renal volume-to-recipient weight ratios (OR = 9.6; 95% CI, 1.8–50.6)ConclusionsPredonation renal volume adjusted to recipient weight may estimate the renal function at discharge and 6 months after transplantation.     

Mammalian Target of Rapamycin Inhibitors Vs Calcineurin Inhibitors in Chronic Graft Rejection After Lung Transplantation: A Systematic Review and Meta‐Analysis

BackgroundThe number of lung transplantations has been rising constantly. However, use of this therapeutic resource is limited by several issues that are difficult to resolve, such as chronic graft rejection and complications secondary to immunosuppression.MethodsThis systematic review compared mammalian target of rapamycin (mTOR) inhibitor immunosuppression associated with low-dose calcineurin inhibitors with isolated calcineurin inhibitor immunosuppression on the new-onset chronic rejection development and mortality 12 months after lung transplantation. Three controlled randomized clinical trials (SHITRIT, NOCTET, and 4EVERLUNG) were selected from electronic databases.ResultsMeta-analysis of the data at 12 months postintervention showed that only 4EVERLUNG assessed chronic graft rejection, with a higher incidence in the control group; however, the difference was not statistically significant (P = .197). Significant data were related to an increase in the number of adverse events (P = .0064) and improved renal function (P < .0001) in the mTOR inhibitor-based scheme. The other outcomes indicated a trend toward greater risk of death and acute graft rejection with the use of mTORs.ConclusionsThe researchers suggest considering the use of mTOR inhibitors, whose greatest benefit is felt by patients with renal dysfunction, in association with the use of calcineurin inhibitors, because of the imminent risk of death among patients with renal failure.     

Clinico-Radiological-Pathologic Profile and Outcomes of Lung Transplant in Post–COVID-19 Phenotype: A Single Center Experience

BackgroundLung transplantation (LTx) has come as hope for select patients with post-COVID acute respiratory distress syndrome (ARDS). It has a different phenotype with unique challenges. We aimed to bring out our experience with and outcomes of LTx for post-COVID ARDS.MethodsThis study is retrospective case series from a single center in India. All the patients with post-COVID end stage lung disease (ESLD) who underwent bilateral LTx between 1st May 2020 and 30th August 2021 were included. LTx was performed following no improvement with optimal medical management with adequate time provided for recovery. Information relating to demographics, comorbidities, pretransplant status, perioperative parameters, gross and histopathological findings of explanted lungs, posttransplant morbidity, and mortality were analyzed.ResultsThis study included 23 patients. The median age of the patients in this study was 42 years and 20 participants were men (87%). The mean duration of intensive care unit stay was 15.83 ± 6.61 days. Mortality was observed among 8 participants (34.78%). Mean survival time was 34.54 weeks. Among the 8 patients who expired, the cause of death was sepsis for 6 patients (75.0%), neurologic cerebrovascular accident for 1 patient (12.5%), and cytomegalovirus for 1 patient (12.5%). All the deaths were reported in primary graft dysfunction grade 2 & 3 category. No rejections were observed on first and third month surveillance biopsies.ConclusionsLTx is the definitive option for survival in select patients with severe post–COVID-19–associated ESLD. This study brings out various challenges involved in such phenotypes and also observations in postoperative recovery.     

Extended-Spectrum Beta-Lactamase–Producing Enterobacteriaceae–Related Urinary Tract Infection in Kidney Transplant Recipients: Risk Factors,Treatment, and Long-Term Outcome

Background

Prevalence of extended-spectrum beta-lactamase–producing Enterobacteriaceae (ESBL-E) has risen in kidney transplant (KT) patients, with no long-term data so far on graft function or survival.

Difficult Balance Between EBV Treatment and Posttransplant Immunosuppression: A Successful Transplant in a Child With Recurrent Epstein-Barr Virus–Induced Hemophagocytic Lymphohistiocytosis

BackgroundHemophagocytic lymphohistiocytosis (HLH) is a rare, life-threatening clinical syndrome. HLH can be classified into 2 major forms: primary and secondary. Viral infections are frequently implicated in the onset of active HLH episodes.Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the only curative treatment for primary HLH and refractory/relapsed HLH after proper chemoimmunotherapy, although following immunosuppressive therapy may lead to infectious complications, including viral infections.Case PresentationWe report a case of a 6-year-old boy with Epstein-Barr virus (EBV)–induced hemophagocytic lymphohistiocytosis. The patient underwent an allo-HSCT from a 10/10 HLA-matched unrelated donor. Because he received myeloablative and immunosuppressive treatment, another EBV reactivation occurred, as well as cytomegalovirus (CMV) reactivation. After antiviral therapy, on day +27, elimination of EBV and CMV was achieved.Repeated chimerism tests evaluated decreasing donor chimerism; graft-versus-host disease prophylaxis was reduced from day +32 and eventually withdrawn.Later on, the patient developed acute graft-versus-host disease (skin rush, gastrointestinal dysfunction). Immunosuppressive agents (methylprednisolone, cyclosporine) were applied once again, which led to an increase of CMV viremia and polyomavirus (BK virus) primary infection.ConclusionsVirus infection can induct a severe disorder, such as HLH, and recur after its treatment. We believe our case represents dynamic changes in immunologic reaction to viral infection, which depend on modifications in treatment after allo-HSCT. These observations underscore the importance and difficulty of balancing immunosuppressive therapy and infection control.